Palovarotene CAS# 410528-02-8 4-[(1E)-2-[5,6,7,8-四氢-5,5,8,8-四甲基-3-(1H-吡唑-1-基甲基)-2-萘基]乙烯基]苯甲酸

Palovarotene, a selective retinoic acid receptor gamma (RARγ) agonist, demonstrates potent bioactivity in preclinical models by targeting the pathogenic signaling in fibrodysplasia ossificans progressiva (FOP) and other heterotopic ossification conditions. In vitro, Palovarotene binds to RARγ with high affinity (Kd in the low nM range) and effectively inhibits chondrogenic differentiation in patient-derived ACVR1(R206H)-mutant cells, reducing expression of key markers like SOX9 and type II collagen by over 50-70% at concentrations as low as 10-100 nM. This anti-chondrogenic activity translates robustly to in vivo models; in the constitutively active Acvr1(Q207D) mouse model of FOP, prophylactic oral administration of Palovarotene (at doses of 1.0 to 5.0 mg/kg/day) reduced heterotopic ossification volume by up to 90% in injury-induced lesions. Similarly, in a mouse model of trauma-induced heterotopic ossification, it significantly decreased ectopic bone formation by inhibiting the cartilaginous anlage, confirming its mechanism of disrupting the aberrant chondrogenesis that precedes bone formation.